Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation.
Type I interferons (IFNs) play an important role in direct antiviral defense as well as linking the innate and adaptive immune responses. On dendritic cells (DCs), IFNs facilitate their activation and contribute to CD8(+) and CD4(+) T cell priming. However, the precise molecular mechanism by which I...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC3883643?pdf=render |
| _version_ | 1818690141448830976 |
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| author | Austin Pantel Angela Teixeira Elias Haddad Elizabeth G Wood Ralph M Steinman M Paula Longhi |
| author_facet | Austin Pantel Angela Teixeira Elias Haddad Elizabeth G Wood Ralph M Steinman M Paula Longhi |
| author_sort | Austin Pantel |
| collection | DOAJ |
| description | Type I interferons (IFNs) play an important role in direct antiviral defense as well as linking the innate and adaptive immune responses. On dendritic cells (DCs), IFNs facilitate their activation and contribute to CD8(+) and CD4(+) T cell priming. However, the precise molecular mechanism by which IFNs regulate maturation and immunogenicity of DCs in vivo has not been studied in depth. Here we show that, after in vivo stimulation with the TLR ligand poly IC, IFNs dominate transcriptional changes in DCs. In contrast to direct TLR3/mda5 signaling, IFNs are required for upregulation of all pathways associated with DC immunogenicity. In addition, metabolic pathways, particularly the switch from oxidative phosphorylation to glycolysis, are also regulated by IFNs and required for DC maturation. These data provide evidence for a metabolic reprogramming concomitant with DC maturation and offer a novel mechanism by which IFNs modulate DC maturation. |
| first_indexed | 2024-12-17T12:21:17Z |
| format | Article |
| id | doaj.art-bb081ee0671843269957b6c90b15fb6d |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-17T12:21:17Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-bb081ee0671843269957b6c90b15fb6d2022-12-21T21:48:57ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852014-01-01121e100175910.1371/journal.pbio.1001759Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation.Austin PantelAngela TeixeiraElias HaddadElizabeth G WoodRalph M SteinmanM Paula LonghiType I interferons (IFNs) play an important role in direct antiviral defense as well as linking the innate and adaptive immune responses. On dendritic cells (DCs), IFNs facilitate their activation and contribute to CD8(+) and CD4(+) T cell priming. However, the precise molecular mechanism by which IFNs regulate maturation and immunogenicity of DCs in vivo has not been studied in depth. Here we show that, after in vivo stimulation with the TLR ligand poly IC, IFNs dominate transcriptional changes in DCs. In contrast to direct TLR3/mda5 signaling, IFNs are required for upregulation of all pathways associated with DC immunogenicity. In addition, metabolic pathways, particularly the switch from oxidative phosphorylation to glycolysis, are also regulated by IFNs and required for DC maturation. These data provide evidence for a metabolic reprogramming concomitant with DC maturation and offer a novel mechanism by which IFNs modulate DC maturation.http://europepmc.org/articles/PMC3883643?pdf=render |
| spellingShingle | Austin Pantel Angela Teixeira Elias Haddad Elizabeth G Wood Ralph M Steinman M Paula Longhi Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. PLoS Biology |
| title | Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. |
| title_full | Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. |
| title_fullStr | Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. |
| title_full_unstemmed | Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. |
| title_short | Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. |
| title_sort | direct type i ifn but not mda5 tlr3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly ic stimulation |
| url | http://europepmc.org/articles/PMC3883643?pdf=render |
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